ArticleMolecular cell2021
Induced intra- and intermolecular template switching as a therapeutic mechanism against RNA viruses.
Article in Molecular cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed.
- GymBuddy and Elomia, AI-integrated applications, effects on the mental health of the students with psychological disorders.BMC psychology · 2025Trial
- The nucleoside analog CMX521 inhibits coronavirus RNA-dependent RNA polymerase via a two-pronged mechanism.bioRxiv : the preprint server for biology · 2026Article
- Copy-back RNA synthesis by coronavirus polymerase requires helicase activity and is stimulated by remdesivir and molnupiravir.Science advances · 2026Article
- Beyond the Single Molecule: Multiplexed Methods in Force Spectroscopy.Annual review of biophysics · 2026Review
- Antiviral candidates for enterovirus 71: targeting viral proteome and stage-specific lifecycle interventions.Virology journal · 2025Review
- Template switching by coronavirus polymerase requires helicase activity and is stimulated by remdesivir and molnupiravir.bioRxiv : the preprint server for biology · 2025Article
- Mechanism of Forced-Copy-Choice RNA Recombination by Enteroviral RNA-Dependent RNA Polymerases.ACS bio & med chem Au · 2025Article
- Subversion of phosphorylated SR proteins by enterovirus A71 in IRES-dependent translation revealed by RNA-interactome analysis.PLoS pathogens · 2025Article
- Antivirotics based on defective interfering particles: emerging concepts and challenges.Frontiers in cellular and infection microbiology · 2025Review
- Molecular basis of RNA recombination in the 3'UTR of chikungunya virus genome.Nucleic acids research · 2024Article
- Novel Anti-Enterovirus A71 Compounds Discovered by Repositioning Antivirals from the Open-Source MMV Pandemic Response Box.Pharmaceuticals (Basel, Switzerland) · 2024Article
- The nucleoside analog 4'-fluorouridine suppresses the replication of multiple enteroviruses by targeting 3D polymerase.Antimicrobial agents and chemotherapy · 2024Article
- Development of Single Molecule Techniques for Sensing and Manipulation of CRISPR and Polymerase Enzymes.Small (Weinheim an der Bergstrasse, Germany) · 2023Review
- The enterovirus genome can be translated in an IRES-independent manner that requires the initiation factors eIF2A/eIF2D.PLoS biology · 2023Article
- Characterizing single-molecule dynamics of viral RNA-dependent RNA polymerases with multiplexed magnetic tweezers.STAR protocols · 2022Article
- Recombination in Positive-Strand RNA Viruses.Frontiers in microbiology · 2022Review
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Authors and funding
17 authors.
Funding
Abstract
Viral RNA-dependent RNA polymerases (RdRps) are a target for broad-spectrum antiviral therapeutic agents. Recently, we demonstrated that incorporation of the T-1106 triphosphate, a pyrazine-carboxamide ribonucleotide, into nascent RNA increases pausing and backtracking by the poliovirus RdRp. Here, by monitoring enterovirus A-71 RdRp dynamics during RNA synthesis using magnetic tweezers, we identify the "backtracked" state as an intermediate used by the RdRp for copy-back RNA synthesis and homologous recombination. Cell-based assays and RNA sequencing (RNA-seq) experiments further demonstrate that the pyrazine-carboxamide ribonucleotide stimulates these processes during infection. These results suggest that pyrazine-carboxamide ribonucleotides do not induce lethal mutagenesis or chain termination but function by promoting template switching and formation of defective viral genomes. We conclude that RdRp-catalyzed intra- and intermolecular template switching can be induced by pyrazine-carboxamide ribonucleotides, defining an additional mechanistic class of antiviral ribonucleotides with potential for broad-spectrum activity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.